|
KMID : 0613820110210081134
|
|
Journal of Life Science
2011 Volume.21 No. 8 p.1134 ~ p.1141
|
|
|
Overexpression of TMP21 Could Induce not only Downregulation of TrkA/ERK Phosphorylation but also Upregulation of p75NTR/RhoA Expression on NGF Receptor Signaling Pathway
|
|
Choi Sun-Il
Jee Seung-Wan
Her Youn-Kyung
Kim Ji-Eun
Nam So-Hee
Hwang In-Sik
Lee Hye-Ryun
Goo Jun-Seo
Lee Young-Ju
Lee Eon-Pil
Choi Hae-Wook
Kim Hong-Sung
Lee Jae-Ho
Jung Young-Jin
Lee Su-Hae
Shim Sun-Bo
Hwang Dae-Youn
|
|
|
Abstract
|
|
|
|
Transmembrane protein 21 (TMP21) is a member of the p24 cargo protein family and has been shown to modulate γ-secretase-mediated Aβ production which was specifically observed in the brains of subjects with Alzheimer’s disease (AD). In order to investigate whether TMP21 could affect nerve growth factor (NGF) receptor signaling pathway, the alteration of NGF receptors and their downstream proteins were detected in TMP21 over-expressed cells. CMV/hTMP21 vector used in this study was successfully expressed into TMP21 proteins in B35 cells after lipofectamin transfection. Expressed TMP21 proteins induced the down-regulation of γ-secretase complex components including Presenlin-1 (PS-1), PS-2, Nicastrin (NST), Pen-2 and APH-1. Also, the expression level of NGF receptor p75NTR and RhoA were significantly higher in CMV/hTMP21 transfectants than vehicle transfectants, while their levels returned to vehicle levels after NGF treatment. However, the phosphorylation of NGF receptor TrkA was dramtically decreased in NGF No-treated CMV/hTMP21 transfectants compared with vehicle transfectants, and increased in NGF treated CMV/hTMP21 transfectants. In TrkA downstream signaling pathway, the phosphorylation level of ERK was also decreased in CMV/hTMP21 transfectants, while the phosphorylation of Akt was increased in the same transfectants. Furthermore, NGF treatment induced the increase of phosphorylation level of Akt and ERK in CMV/hTMP21 transfectants. Therefore, these results suggested that over-expression of TMP21 may simultaneously induce the up-regulation of p75NTR/RhoA expression and the down-regulation of TrkA/ERK phosphorylation through the inhibition of γ-secretase activity.
|
|
|
KEYWORD
|
|
|
Alzheimer’s disease, transmembrane protein 21(TMP21), nerve growth factors(NGF) receptor, p75NTR, TrkA
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|